Changes of GABA receptors and dopamine turnover in the postmortem brains of parkinsonians with levodopa-induced motor complications
Identifieur interne : 000971 ( PascalFrancis/Checkpoint ); précédent : 000970; suivant : 000972Changes of GABA receptors and dopamine turnover in the postmortem brains of parkinsonians with levodopa-induced motor complications
Auteurs : Frédéric Calon [Canada] ; Marc Morissette [Canada] ; Ali H. Rajput [Canada] ; Oleh Hornykiewicz [Canada, Autriche] ; Paul J. Bedard [Canada] ; Thérèse Di Paolo [Canada]Source :
- Movement disorders [ 0885-3185 ] ; 2003.
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Abstract
Brain samples from 14 Parkinson's disease patients, 10 of whom developed motor complications (dyskinesias and/or wearing-off) on dopaminomimetic therapy, and 11 controls were analyzed. Striatal 3β-(4-125I-iodophenyl)tropane-2β-carboxylic acid isopropyl ester ([125I]RTI-121)-specific binding to dopamine transporter and concentration of dopamine were markedly decreased, but no association between level of denervation and development of motor complications was observed. The homovanillic acid/dopamine ratio of concentrations was higher in putamen of patients with wearing-off compared to those without. Striatal 35S-labeled t-butylbicyclophosphorothionate ([35S]TBPS) and [3H]flunitrazepam binding to GABAA receptors were unchanged in patients with Parkinsons disease, whereas [125I]CGP 64213 -specific binding to GABAB receptors was decreased in the putamen and external segment of the globus pallidus of parkinsonian patients compared with controls. [3H]Flunitrazepam binding was increased in the putamen of patients with wearing-off compared to those without. [35S]TBPS-specific binding was increased in the ventral internal globus pallidus of dyskinetic subjects. These data suggest altered dopamine metabolism and increased GABAA receptors in the putamen related to the pathophysiology of wearing-off. The present results also suggest that an up-regulation of GABAA receptors in the internal globus pallidus is linked to the pathogenesis of levodopa-induced dyskinesias.
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Bedard</name><affiliation wicri:level="1"><inist:fA14 i1="04"><s1>Neuroscience Research Unit, Laval University Medical Center (CHUL), and Department of Medicine, Faculty of Medicine, Laval University</s1><s2>Québec</s2><s3>CAN</s3><sZ>5 aut.</sZ></inist:fA14><country>Canada</country><wicri:noRegion>Québec</wicri:noRegion></affiliation></author><author><name sortKey="Di Paolo, Therese" sort="Di Paolo, Therese" uniqKey="Di Paolo T" first="Thérèse" last="Di Paolo">Thérèse Di Paolo</name><affiliation wicri:level="1"><inist:fA14 i1="01"><s1>Molecular Endocrinology and Oncology Research Center, Laval University Medical Center (CHUL), and Faculty of Pharmacy, Laval University</s1><s2>Québec</s2><s3>CAN</s3><sZ>1 aut.</sZ><sZ>2 aut.</sZ><sZ>6 aut.</sZ></inist:fA14><country>Canada</country><wicri:noRegion>Québec</wicri:noRegion></affiliation></author></titleStmt><publicationStmt><idno type="wicri:source">INIST</idno><idno type="inist">03-0238134</idno><date when="2003">2003</date><idno type="stanalyst">PASCAL 03-0238134 INIST</idno><idno type="RBID">Pascal:03-0238134</idno><idno type="wicri:Area/PascalFrancis/Corpus">000A79</idno><idno type="wicri:Area/PascalFrancis/Curation">000244</idno><idno type="wicri:Area/PascalFrancis/Checkpoint">000971</idno><idno type="wicri:explorRef" wicri:stream="PascalFrancis" wicri:step="Checkpoint">000971</idno></publicationStmt><sourceDesc><biblStruct><analytic><title xml:lang="en" level="a">Changes of GABA receptors and dopamine turnover in the postmortem brains of parkinsonians with levodopa-induced motor complications</title><author><name sortKey="Calon, Frederic" sort="Calon, Frederic" uniqKey="Calon F" first="Frédéric" last="Calon">Frédéric Calon</name><affiliation wicri:level="1"><inist:fA14 i1="01"><s1>Molecular Endocrinology and Oncology Research Center, Laval University Medical Center (CHUL), and Faculty of Pharmacy, Laval University</s1><s2>Québec</s2><s3>CAN</s3><sZ>1 aut.</sZ><sZ>2 aut.</sZ><sZ>6 aut.</sZ></inist:fA14><country>Canada</country><wicri:noRegion>Québec</wicri:noRegion></affiliation></author><author><name sortKey="Morissette, Marc" sort="Morissette, Marc" uniqKey="Morissette M" first="Marc" last="Morissette">Marc Morissette</name><affiliation wicri:level="1"><inist:fA14 i1="01"><s1>Molecular Endocrinology and Oncology Research Center, Laval University Medical Center (CHUL), and Faculty of Pharmacy, Laval University</s1><s2>Québec</s2><s3>CAN</s3><sZ>1 aut.</sZ><sZ>2 aut.</sZ><sZ>6 aut.</sZ></inist:fA14><country>Canada</country><wicri:noRegion>Québec</wicri:noRegion></affiliation></author><author><name sortKey="Rajput, Ali H" sort="Rajput, Ali H" uniqKey="Rajput A" first="Ali H." last="Rajput">Ali H. Rajput</name><affiliation wicri:level="1"><inist:fA14 i1="02"><s1>Division of Neurology, University of Saskatchewan, Royal University Hospital</s1><s2>Saskatoon</s2><s3>CAN</s3><sZ>3 aut.</sZ><sZ>4 aut.</sZ></inist:fA14><country>Canada</country><wicri:noRegion>Saskatoon</wicri:noRegion></affiliation></author><author><name sortKey="Hornykiewicz, Oleh" sort="Hornykiewicz, Oleh" uniqKey="Hornykiewicz O" first="Oleh" last="Hornykiewicz">Oleh Hornykiewicz</name><affiliation wicri:level="1"><inist:fA14 i1="02"><s1>Division of Neurology, University of Saskatchewan, Royal University Hospital</s1><s2>Saskatoon</s2><s3>CAN</s3><sZ>3 aut.</sZ><sZ>4 aut.</sZ></inist:fA14><country>Canada</country><wicri:noRegion>Saskatoon</wicri:noRegion></affiliation><affiliation wicri:level="3"><inist:fA14 i1="03"><s1>Institute for Brain Research, Faculty of Medicine, University of Vienna</s1><s2>Vienna</s2><s3>AUT</s3><sZ>4 aut.</sZ></inist:fA14><country>Autriche</country><placeName><settlement type="city">Vienne (Autriche)</settlement><region nuts="2" type="province">Vienne (Autriche)</region></placeName></affiliation></author><author><name sortKey="Bedard, Paul J" sort="Bedard, Paul J" uniqKey="Bedard P" first="Paul J." last="Bedard">Paul J. Bedard</name><affiliation wicri:level="1"><inist:fA14 i1="04"><s1>Neuroscience Research Unit, Laval University Medical Center (CHUL), and Department of Medicine, Faculty of Medicine, Laval University</s1><s2>Québec</s2><s3>CAN</s3><sZ>5 aut.</sZ></inist:fA14><country>Canada</country><wicri:noRegion>Québec</wicri:noRegion></affiliation></author><author><name sortKey="Di Paolo, Therese" sort="Di Paolo, Therese" uniqKey="Di Paolo T" first="Thérèse" last="Di Paolo">Thérèse Di Paolo</name><affiliation wicri:level="1"><inist:fA14 i1="01"><s1>Molecular Endocrinology and Oncology Research Center, Laval University Medical Center (CHUL), and Faculty of Pharmacy, Laval University</s1><s2>Québec</s2><s3>CAN</s3><sZ>1 aut.</sZ><sZ>2 aut.</sZ><sZ>6 aut.</sZ></inist:fA14><country>Canada</country><wicri:noRegion>Québec</wicri:noRegion></affiliation></author></analytic><series><title level="j" type="main">Movement disorders</title><title level="j" type="abbreviated">Mov. disord.</title><idno type="ISSN">0885-3185</idno><imprint><date when="2003">2003</date></imprint></series></biblStruct></sourceDesc><seriesStmt><title level="j" type="main">Movement disorders</title><title level="j" type="abbreviated">Mov. disord.</title><idno type="ISSN">0885-3185</idno></seriesStmt></fileDesc><profileDesc><textClass><keywords scheme="KwdEn" xml:lang="en"><term>Antiparkinson agent</term><term>Autoradiography</term><term>Biological transport</term><term>Catecholamine</term><term>Chemotherapy</term><term>Dopamine</term><term>Dyskinesia</term><term>Gabaergic receptor</term><term>Human</term><term>Levodopa</term><term>Mechanism of action</term><term>Metabolism</term><term>Parkinson disease</term><term>Toxicity</term><term>Treatment</term></keywords><keywords scheme="Pascal" xml:lang="fr"><term>Parkinson maladie</term><term>Récepteur gabaergique</term><term>Autoradiographie</term><term>Dopamine</term><term>Transport biologique</term><term>Catécholamine</term><term>Dyskinésie</term><term>Lévodopa</term><term>Chimiothérapie</term><term>Antiparkinsonien</term><term>Mécanisme action</term><term>Traitement</term><term>Toxicité</term><term>Métabolisme</term><term>Homme</term></keywords><keywords scheme="Wicri" type="topic" xml:lang="fr"><term>Homme</term></keywords></textClass></profileDesc></teiHeader><front><div type="abstract" xml:lang="en">Brain samples from 14 Parkinson's disease patients, 10 of whom developed motor complications (dyskinesias and/or wearing-off) on dopaminomimetic therapy, and 11 controls were analyzed. Striatal 3β-(4-<sup>125</sup>I-iodophenyl)tropane-2β-carboxylic acid isopropyl ester ([<sup>125</sup>I]RTI-121)-specific binding to dopamine transporter and concentration of dopamine were markedly decreased, but no association between level of denervation and development of motor complications was observed. The homovanillic acid/dopamine ratio of concentrations was higher in putamen of patients with wearing-off compared to those without. Striatal <sup>35</sup>S-labeled t-butylbicyclophosphorothionate ([<sup>35</sup>S]TBPS) and [<sup>3</sup>H]flunitrazepam binding to GABA<sub>A</sub> receptors were unchanged in patients with Parkinsons disease, whereas [<sup>125</sup>I]CGP 64213 -specific binding to GABA<sub>B</sub> receptors was decreased in the putamen and external segment of the globus pallidus of parkinsonian patients compared with controls. [<sup>3</sup>H]Flunitrazepam binding was increased in the putamen of patients with wearing-off compared to those without. [<sup>35</sup>S]TBPS-specific binding was increased in the ventral internal globus pallidus of dyskinetic subjects. These data suggest altered dopamine metabolism and increased GABA<sub>A</sub> receptors in the putamen related to the pathophysiology of wearing-off. The present results also suggest that an up-regulation of GABA<sub>A</sub> receptors in the internal globus pallidus is linked to the pathogenesis of levodopa-induced dyskinesias.</div></front></TEI><inist><standard h6="B"><pA><fA01 i1="01" i2="1"><s0>0885-3185</s0></fA01><fA03 i2="1"><s0>Mov. disord.</s0></fA03><fA05><s2>18</s2></fA05><fA06><s2>3</s2></fA06><fA08 i1="01" i2="1" l="ENG"><s1>Changes of GABA receptors and dopamine turnover in the postmortem brains of parkinsonians with levodopa-induced motor complications</s1></fA08><fA11 i1="01" i2="1"><s1>CALON (Frédéric)</s1></fA11><fA11 i1="02" i2="1"><s1>MORISSETTE (Marc)</s1></fA11><fA11 i1="03" i2="1"><s1>RAJPUT (Ali H.)</s1></fA11><fA11 i1="04" i2="1"><s1>HORNYKIEWICZ (Oleh)</s1></fA11><fA11 i1="05" i2="1"><s1>BEDARD (Paul J.)</s1></fA11><fA11 i1="06" i2="1"><s1>DI PAOLO (Thérèse)</s1></fA11><fA14 i1="01"><s1>Molecular Endocrinology and Oncology Research Center, Laval University Medical Center (CHUL), and Faculty of Pharmacy, Laval University</s1><s2>Québec</s2><s3>CAN</s3><sZ>1 aut.</sZ><sZ>2 aut.</sZ><sZ>6 aut.</sZ></fA14><fA14 i1="02"><s1>Division of Neurology, University of Saskatchewan, Royal University Hospital</s1><s2>Saskatoon</s2><s3>CAN</s3><sZ>3 aut.</sZ><sZ>4 aut.</sZ></fA14><fA14 i1="03"><s1>Institute for Brain Research, Faculty of Medicine, University of Vienna</s1><s2>Vienna</s2><s3>AUT</s3><sZ>4 aut.</sZ></fA14><fA14 i1="04"><s1>Neuroscience Research Unit, Laval University Medical Center (CHUL), and Department of Medicine, Faculty of Medicine, Laval University</s1><s2>Québec</s2><s3>CAN</s3><sZ>5 aut.</sZ></fA14><fA20><s1>241-253</s1></fA20><fA21><s1>2003</s1></fA21><fA23 i1="01"><s0>ENG</s0></fA23><fA43 i1="01"><s1>INIST</s1><s2>20953</s2><s5>354000109859510020</s5></fA43><fA44><s0>0000</s0><s1>© 2003 INIST-CNRS. All rights reserved.</s1></fA44><fA45><s0>85 ref.</s0></fA45><fA47 i1="01" i2="1"><s0>03-0238134</s0></fA47><fA60><s1>P</s1></fA60><fA61><s0>A</s0></fA61><fA64 i1="01" i2="1"><s0>Movement disorders</s0></fA64><fA66 i1="01"><s0>USA</s0></fA66><fC01 i1="01" l="ENG"><s0>Brain samples from 14 Parkinson's disease patients, 10 of whom developed motor complications (dyskinesias and/or wearing-off) on dopaminomimetic therapy, and 11 controls were analyzed. Striatal 3β-(4-<sup>125</sup>I-iodophenyl)tropane-2β-carboxylic acid isopropyl ester ([<sup>125</sup>I]RTI-121)-specific binding to dopamine transporter and concentration of dopamine were markedly decreased, but no association between level of denervation and development of motor complications was observed. The homovanillic acid/dopamine ratio of concentrations was higher in putamen of patients with wearing-off compared to those without. Striatal <sup>35</sup>S-labeled t-butylbicyclophosphorothionate ([<sup>35</sup>S]TBPS) and [<sup>3</sup>H]flunitrazepam binding to GABA<sub>A</sub> receptors were unchanged in patients with Parkinsons disease, whereas [<sup>125</sup>I]CGP 64213 -specific binding to GABA<sub>B</sub> receptors was decreased in the putamen and external segment of the globus pallidus of parkinsonian patients compared with controls. [<sup>3</sup>H]Flunitrazepam binding was increased in the putamen of patients with wearing-off compared to those without. [<sup>35</sup>S]TBPS-specific binding was increased in the ventral internal globus pallidus of dyskinetic subjects. These data suggest altered dopamine metabolism and increased GABA<sub>A</sub> receptors in the putamen related to the pathophysiology of wearing-off. The present results also suggest that an up-regulation of GABA<sub>A</sub> receptors in the internal globus pallidus is linked to the pathogenesis of levodopa-induced dyskinesias.</s0></fC01><fC02 i1="01" i2="X"><s0>002B02U01</s0></fC02><fC03 i1="01" i2="X" l="FRE"><s0>Parkinson maladie</s0><s5>01</s5></fC03><fC03 i1="01" i2="X" l="ENG"><s0>Parkinson disease</s0><s5>01</s5></fC03><fC03 i1="01" i2="X" l="SPA"><s0>Parkinson enfermedad</s0><s5>01</s5></fC03><fC03 i1="02" i2="X" l="FRE"><s0>Récepteur gabaergique</s0><s5>04</s5></fC03><fC03 i1="02" i2="X" l="ENG"><s0>Gabaergic receptor</s0><s5>04</s5></fC03><fC03 i1="02" i2="X" l="SPA"><s0>Receptor gabaminérgico</s0><s5>04</s5></fC03><fC03 i1="03" i2="X" l="FRE"><s0>Autoradiographie</s0><s5>05</s5></fC03><fC03 i1="03" i2="X" l="ENG"><s0>Autoradiography</s0><s5>05</s5></fC03><fC03 i1="03" i2="X" l="SPA"><s0>Autorradiografía</s0><s5>05</s5></fC03><fC03 i1="04" i2="X" l="FRE"><s0>Dopamine</s0><s2>NK</s2><s2>FR</s2><s5>07</s5></fC03><fC03 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l="SPA"><s0>Levodopa</s0><s2>NK</s2><s2>FR</s2><s5>13</s5></fC03><fC03 i1="09" i2="X" l="FRE"><s0>Chimiothérapie</s0><s5>14</s5></fC03><fC03 i1="09" i2="X" l="ENG"><s0>Chemotherapy</s0><s5>14</s5></fC03><fC03 i1="09" i2="X" l="SPA"><s0>Quimioterapia</s0><s5>14</s5></fC03><fC03 i1="10" i2="X" l="FRE"><s0>Antiparkinsonien</s0><s5>15</s5></fC03><fC03 i1="10" i2="X" l="ENG"><s0>Antiparkinson agent</s0><s5>15</s5></fC03><fC03 i1="10" i2="X" l="SPA"><s0>Antiparkinsoniano</s0><s5>15</s5></fC03><fC03 i1="11" i2="X" l="FRE"><s0>Mécanisme action</s0><s5>16</s5></fC03><fC03 i1="11" i2="X" l="ENG"><s0>Mechanism of action</s0><s5>16</s5></fC03><fC03 i1="11" i2="X" l="SPA"><s0>Mecanismo acción</s0><s5>16</s5></fC03><fC03 i1="12" i2="X" l="FRE"><s0>Traitement</s0><s5>17</s5></fC03><fC03 i1="12" i2="X" l="ENG"><s0>Treatment</s0><s5>17</s5></fC03><fC03 i1="12" i2="X" l="SPA"><s0>Tratamiento</s0><s5>17</s5></fC03><fC03 i1="13" i2="X" l="FRE"><s0>Toxicité</s0><s5>18</s5></fC03><fC03 i1="13" i2="X" l="ENG"><s0>Toxicity</s0><s5>18</s5></fC03><fC03 i1="13" i2="X" l="SPA"><s0>Toxicidad</s0><s5>18</s5></fC03><fC03 i1="14" i2="X" l="FRE"><s0>Métabolisme</s0><s5>19</s5></fC03><fC03 i1="14" i2="X" l="ENG"><s0>Metabolism</s0><s5>19</s5></fC03><fC03 i1="14" i2="X" l="SPA"><s0>Metabolismo</s0><s5>19</s5></fC03><fC03 i1="15" i2="X" l="FRE"><s0>Homme</s0><s5>20</s5></fC03><fC03 i1="15" i2="X" l="ENG"><s0>Human</s0><s5>20</s5></fC03><fC03 i1="15" i2="X" l="SPA"><s0>Hombre</s0><s5>20</s5></fC03><fC07 i1="01" i2="X" l="FRE"><s0>Système nerveux pathologie</s0><s5>37</s5></fC07><fC07 i1="01" i2="X" l="ENG"><s0>Nervous system diseases</s0><s5>37</s5></fC07><fC07 i1="01" i2="X" l="SPA"><s0>Sistema nervioso patología</s0><s5>37</s5></fC07><fC07 i1="02" i2="X" l="FRE"><s0>Système nerveux central pathologie</s0><s5>38</s5></fC07><fC07 i1="02" i2="X" l="ENG"><s0>Central nervous system disease</s0><s5>38</s5></fC07><fC07 i1="02" i2="X" l="SPA"><s0>Sistema nervosio central patología</s0><s5>38</s5></fC07><fC07 i1="03" i2="X" l="FRE"><s0>Encéphale pathologie</s0><s5>39</s5></fC07><fC07 i1="03" i2="X" l="ENG"><s0>Cerebral disorder</s0><s5>39</s5></fC07><fC07 i1="03" i2="X" l="SPA"><s0>Encéfalo patología</s0><s5>39</s5></fC07><fC07 i1="04" i2="X" l="FRE"><s0>Extrapyramidal syndrome</s0><s5>40</s5></fC07><fC07 i1="04" i2="X" l="ENG"><s0>Extrapyramidal syndrome</s0><s5>40</s5></fC07><fC07 i1="04" i2="X" l="SPA"><s0>Extrapiramidal síndrome</s0><s5>40</s5></fC07><fC07 i1="05" i2="X" l="FRE"><s0>Maladie dégénérative</s0><s5>41</s5></fC07><fC07 i1="05" i2="X" l="ENG"><s0>Degenerative disease</s0><s5>41</s5></fC07><fC07 i1="05" i2="X" l="SPA"><s0>Enfermedad degenerativa</s0><s5>41</s5></fC07><fC07 i1="06" i2="X" l="FRE"><s0>Mouvement involontaire</s0><s5>61</s5></fC07><fC07 i1="06" i2="X" l="ENG"><s0>Involuntary movement</s0><s5>61</s5></fC07><fC07 i1="06" i2="X" l="SPA"><s0>Movimiento involuntario</s0><s5>61</s5></fC07><fC07 i1="07" i2="X" l="FRE"><s0>Trouble neurologique</s0><s5>62</s5></fC07><fC07 i1="07" i2="X" l="ENG"><s0>Neurological disorder</s0><s5>62</s5></fC07><fC07 i1="07" i2="X" l="SPA"><s0>Trastorno neurológico</s0><s5>62</s5></fC07><fC07 i1="08" i2="X" l="FRE"><s0>Trouble moteur</s0><s5>63</s5></fC07><fC07 i1="08" i2="X" l="ENG"><s0>Motor system disorder</s0><s5>63</s5></fC07><fC07 i1="08" i2="X" l="SPA"><s0>Trastorno motor</s0><s5>63</s5></fC07><fN21><s1>146</s1></fN21><fN82><s1>PSI</s1></fN82></pA></standard></inist><affiliations><list><country><li>Autriche</li><li>Canada</li></country><region><li>Vienne (Autriche)</li></region><settlement><li>Vienne (Autriche)</li></settlement></list><tree><country name="Canada"><noRegion><name sortKey="Calon, Frederic" sort="Calon, Frederic" uniqKey="Calon F" first="Frédéric" last="Calon">Frédéric Calon</name></noRegion><name sortKey="Bedard, Paul J" sort="Bedard, Paul J" uniqKey="Bedard P" first="Paul J." last="Bedard">Paul J. Bedard</name><name sortKey="Di Paolo, Therese" sort="Di Paolo, Therese" uniqKey="Di Paolo T" first="Thérèse" last="Di Paolo">Thérèse Di Paolo</name><name sortKey="Hornykiewicz, Oleh" sort="Hornykiewicz, Oleh" uniqKey="Hornykiewicz O" first="Oleh" last="Hornykiewicz">Oleh Hornykiewicz</name><name sortKey="Morissette, Marc" sort="Morissette, Marc" uniqKey="Morissette M" first="Marc" last="Morissette">Marc Morissette</name><name sortKey="Rajput, Ali H" sort="Rajput, Ali H" uniqKey="Rajput A" first="Ali H." last="Rajput">Ali H. Rajput</name></country><country name="Autriche"><region name="Vienne (Autriche)"><name sortKey="Hornykiewicz, Oleh" sort="Hornykiewicz, Oleh" uniqKey="Hornykiewicz O" first="Oleh" last="Hornykiewicz">Oleh Hornykiewicz</name></region></country></tree></affiliations></record>Pour manipuler ce document sous Unix (Dilib)
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|texte= Changes of GABA receptors and dopamine turnover in the postmortem brains of parkinsonians with levodopa-induced motor complications
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